PROJECT B: HT and Risk of Non-Hodgkin's Lymphoma (NHL). NHL rates have been increasing since the 1940s. Incidence is lower among women than among men, yet few risk factors explain the incidence patterns. One possible exposure that may explain differences in risk patterns between men and women is hormone therapy (HT). Our prior research suggested that HT and other exogenous estrogen exposures decrease women's risk of high and intermediate grade NHL, yet results of another study suggest HT increases risk of follicular NHL (a type that we did not study). Both studies had limited information on potential confounders of an HT-NHL relationship; nevertheless these results are intriguing because a preponderance of evidence suggests that HT suppresses secretion of interleukin-6 (IL-6), a potent B-cell growth factor that is elevated in untreated NHL patients. Other studies have shown that estrogen-estrogen receptor complexes bind directly to a site in the IL-6 promoter region and reduce IL-6 production. Functional polymorphisms have been described in the IL-6 promoter that regulate IL-6 production and the haplotype structure has been defined. We propose to study the effect of HT on NHL risk and the possible effect of IL-6 genotypes and haplotypes on this relationship. We will accomplish these aims by conducting apopulation- based case-control study of B-cell NHL among women 45-79 years of age, living in Los Angeles County, who are English-speaking. We will recruit 1060 cases and 1060 matched controls, who will provide detailed information on HT and various other exposures in a personal interview as well as DNA via buccal cell sample. Cases will be identified using rapid case ascertainment through Core B. Controls will be identified through Core D and will be matched to cases on age, race/ethnicity, and socioeconomic status based on mean income and education level of their neighborhood. In this study, we will address: 1) whether HT use (by duration, formulation, age and recency of use) affects NHL risk; 2) whether NHL risk associated with HT use varies by major NHL subtype; 3) whether IL-6 genotype/haplotype (measured by Core C) modifies these relationships; and 4) whether OC use, reproductive factors, medical exposures or other lifestyle characteristics influence risk of NHL.